Home FOR AUTHORS Endocrine Regulations 2013 Endocrine Regulations Vol.47, No.1, p.15–26, 2013

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Quarterly, 50 pp. per issue 
Founded: 1967
ISSN 1210-0668
E-ISSN 1336-0329

Published in English

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Endocrine Regulations Vol.47, No.1, p.15–26, 2013

Title: Insulin receptor, IRS1, IRS2, INSIG1, INSIG2, RRAD, and BAIAP2 gene expressions in glioma U87 cells with ERN1 loss of function: effect of hypoxia and glutamine or glucose deprivation
Author: D. O. Minchenko, A. P. Kharkova, O. V. Hubenia, O. H. Minchenko

Abstract: Objective. The purpose of this study was to examine: 1) the association between the expression of the insulin receptor (INSR), insulin receptor substrate 1 (IRS1) and 2 (IRS2), insulin inducible gene 1 (INSIG1) and 2 (INSIG2), Ras-related associated with diabetes (RRAD), and brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) genes in glioma cells and 2) the function of the endoplasmic reticulum stress signaling, mediated by endoplasmic reticulum to nuclei-1 (ERN1) and regulation of these gene expressions by hypoxia and glucose or glutamine deprivation.
Methods. The expression of the INSR, IRS1, IRS2, INSIG1, INSIG2, RRAD, and BAIAP2 genes in the glioma cell line U87 and its subline with ERN1 loss of function was studied by qPCR. The cells were exposed to a mix of 3 % oxygen and 5 % carbon dioxide and glucose or glutamine deprivation.
Results. The blockade of the ERN1 signaling enzyme function in glioma cells leads to the gene expression increase in INSR, INSIG2, and IRS2 and decrease in the BAIAP2 and RRAD genes. Hypoxia affected the expression of the INSR, IRS1, IRS2, INSIG1, INSIG2, and BAIAP2 genes with more significant changes in INSIG2 and IRS2 genes. Furthermore, the effect of hypoxia on expression of these genes was mostly dependent on the ERN1 signaling enzyme function. The data also show that glucose or glutamine deprivation may change the expression of the genes studied and that the suppression of the ERN1 enzyme function usually modifies the effect of the glucose or glutamine deprivation.
Conclusions. Results of this study demonstrated the dependence of INSR and related to insulin receptor signaling gene expressions in U87 glioma cells on ERN1 enzyme function indicating its participation in the regulation of metabolic and proliferative processes via endoplasmic reticulum stress which is important component of tumor growth and metabolic diseases. Moreover, hypoxia and glucose or glutamine deprivation are controlled by the expression of insulin receptor and related to insulin signaling genes mostly via ERN1 enzyme signaling.

Keywords: insulin receptor, IRS2, INSIG2, gene expressions, glioma U87 cells, ERN1, hypoxia, glucose deprivation
Year: 2013, Volume: 47, Issue: 1 Page From: 15, Page To: 26
doi:10.4149/endo_2013_01_15
Price: 24.00 €






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